[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Sun, Lihua; Aarnio, Richard; Herre, Erika Atencio; Kärnä, Salli; Palani, Senthil; Virtanen, Helena E.; Liljenbäck, Heidi; Virta, Jenni; Honkaniemi, Aake; Oikonen, Vesa; Han, Chunlei; Laurila, Sanna; Bucci, Marco; Helin, Semi; Yatkin, Emrah; Nummenmaa, Lauri; Nuutila, Pirjo; Tang, Jing; Roivainen, Anne

doi:10.1007/s00259-022-05969-5

Cited by 8 publications

(4 citation statements)

References 32 publications

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“…Previously, [ 11 C]CFN PET studies have administered > 200 ng/kg CFN mass to rats 18 , while other studies did not report information regarding mass injected 19 , 20 . Recently, two additional rat [ 11 C]CFN PET studies constrained the injected mass to below 100 ng/kg 21 and 30 ng/kg 22 , respectively. In general, FDA mandates quality analysis prior to tracer administration in clinical PET studies despite the short half-life of C-11 (20.4 min), which allows one to tightly control the injection mass of [ 11 C]CFN for human safety.…”

Section: Discussionmentioning

confidence: 99%

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain

Kelleher,

Pearson,

Ramsey

et al. 2024

Sci Rep

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Abstract[11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained < 40 ng/kg (~ 10% MOR occupancy in rats), baseline MOR availability was significantly decreased. For test–retest variability (TRTV), better reproducibility was achieved by controlling CFN injected mass to limit the difference between scans. Taken together, we report significant cardiorespiratory depression and a paradoxical influence on baseline MOR availability at conventional tracer doses in rats. Our findings might reflect changes in cerebral blood flow, changes in receptor affinity, or receptor internalization, and merits further mechanistic investigation. In conclusion, rat [11C]CFN PET requires stringent quality assurance of radiotracer synthesis and mass injected to avoid pharmacological effects and limit potential influences on MOR quantification and reproducibility.

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Section: Discussionmentioning

confidence: 99%

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain

Kelleher,

Pearson,

Ramsey

et al. 2024

Sci Rep

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“…Clinical in vivo data also indicates a light-sensitive fluctuation in levels of cerebral monoamine oxidase A, an enzyme that degrades neurotransmitters including serotonin and dopamine (Spies et al, 2018). Similarly, a paucity of studies on neuropeptide signaling suggest that the endogenous opioid signaling responds to seasonal rhythms (Sun et al, 2021; Sun et al, 2022). The present results on dopamine receptor signaling further highlight the brain neurotransmission mechanism on seasonal patterns of cognitive and affective functions.…”

Section: Discussionmentioning

confidence: 99%

Seasonal variation in D2/3 dopamine receptor availability in the human brain

Sun,

Malén,

Tuisku

et al. 2023

Preprint

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Brain functional and physiological plasticity is essential to combat dynamic environmental challenges. The rhythmicin vivodopamine signaling pathway, which regulates emotion, reward and learning, shows seasonal patterns with higher capacity of dopamine synthesis and lower number of dopamine transporters during dark seasons. However, seasonal variation of the dopamine receptor signaling remains to be characterized. Here, based on historical database of healthy human brain [11C]raclopride PET scans (n = 291, 224 males and 67 females), we investigated the seasonal patterns of D2/3 dopamine receptor signaling. We found that daylength at the time of scanning was negatively correlated with availability of this type of receptors in the striatum. Likely, seasonally varying D2/3 receptor signaling also underlies the seasonality of mood, feeding, and motivational processes.Significance of the studyBrainin vivoneurotransmitter signaling demonstrates seasonal patterns. The dopamine D2/3 receptor, with both pre- and postsynaptic expressions, has been targeted by major antipsychotic and antiparkinsonian pharmaceuticals. The current study, based on a large dataset of healthy brain PET images quantifying these receptors, shows that dark seasons are associated with increased receptor availability in the striatum. Considering the previous findings of increased dopamine synthesis and lowered number of transporters, findings may suggest elevated presynaptic control of dopamine release and increased dopamine receptor sensitivity during dark seasons. The rhythmic D2/3 receptor availability may be a mechanism underlying seasonality in mood, feeding, and motivational processes.

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“…7 Mechanism of the secretin-induced satiation. BOLD, bloodoxygen-level-dependent signal supporting a potential role of central opioid signaling in BAT thermogenesis [37]. However, whether these neurotransmission signaling pathways are involved in secretinmediated BAT-caudate crosstalk, subsequently associative to satiation, remains to be explored.…”

Section: Satiation Secretinmentioning

confidence: 99%

Secretin modulates appetite via brown adipose tissue-brain axis

Sun

Laurila

Lahesmaa

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown. Methods and results In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation. Conclusion These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity. Trial registration EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.

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[11C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue

Cited by 8 publications

References 32 publications

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain

Investigation of [11C]carfentanil for mu opioid receptor quantification in the rat brain

Seasonal variation in D2/3 dopamine receptor availability in the human brain

Secretin modulates appetite via brown adipose tissue-brain axis

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